We propose to extend an ongoing pilot investigation of tryptophan metabolism in a population of disturbed children and young adults exhibiting high blood levels of serotonin (hyperserotonemia) in order to elucidate the physiological or biochemical mechanisms accounting for these elevated levels. We will pursue both in-depth studies in selected hyperserotonemic individuals as well as more global investigations of populations with possible hyperserotonemia. In-depth studies will include determining blood and urinary metabolites of tryptophan in hyperserotonemic individuals, as well as determining simultaneously blood and urinary measures of tryptophan metabolism following administration of a tryptophan load. We will investigate amino acid abnormalities as well as primary platelet abnormalities which could result in increased levels of blood serotonin. To gain a better global understanding of the meaning and mechanism(s) of hyperserotonemia we propose to investigate these measures in two currently discovered types of hyperserotonemia, type A and type B. Blood serotonin will be determined in parents and siblings of hyperserotonemic and "normal blood serotonin" children to investigate familial links of hyperserotonemia. Finally we propose to extend our screening for the presence of hyperserotonemia to include other patient and normal populations. Blood and urinary measurements of tryptophan metabolites will be measured in part with high-pressure liquid chromatography (HPLC) and/or column chromatography and solvent extraction procedures.